chr19-51387258-G-A

Position:

• chr19-51387258-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000596399.2(LIM2):​c.175+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,614,102 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0076 (19 hom., cov: 32)
  • Exomes 𝑓: 0.00080 (21 hom.)
• Consequence: LIM2 ENST00000596399.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.06

Genes affected

LIM2 (HGNC:6610): (lens intrinsic membrane protein 2) This gene encodes an eye lens-specific protein found at the junctions of lens fiber cells, where it may contribute to cell junctional organization. It acts as a receptor for calmodulin, and may play an important role in both lens development and cataractogenesis. Mutations in this gene have been associated with cataract formation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

LIM2-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 19-51387258-G-A is Benign according to our data. Variant chr19-51387258-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 702391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-51387258-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00761 (1159/152314) while in subpopulation AFR AF= 0.0268 (1115/41566). AF 95% confidence interval is 0.0255. There are 19 homozygotes in gnomad4. There are 551 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 19 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIM2	NM_001161748.2	c.175+11C>T		intron_variant		ENST00000596399.2	NP_001155220.1
LIM2-AS1	XR_002958397.2	n.91-30G>A		intron_variant, non_coding_transcript_variant
LIM2	NM_030657.4	c.186C>T	p.Pro62=	synonymous_variant	2/5		NP_085915.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIM2	ENST00000221973.7	c.186C>T	p.Pro62=	synonymous_variant	2/5	1		ENSP00000221973
LIM2	ENST00000596399.2	c.175+11C>T		intron_variant		1	NM_001161748.2	ENSP00000472090	P1

Frequencies

GnomAD3 genomes AF: 0.00759 AC: 1155 AN: 152196 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00765

GnomAD3 exomes AF: 0.00183 AC: 459 AN: 251128 Hom.: 12 AF XY: 0.00138 AC XY: 187 AN XY: 135834

Gnomad AFR exome AF: 0.0254

Gnomad AMR exome AF: 0.000694

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000969

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000799 AC: 1168 AN: 1461788 Hom.: 21 Cov.: 33 AF XY: 0.000705 AC XY: 513 AN XY: 727200

Gnomad4 AFR exome AF: 0.0267

Gnomad4 AMR exome AF: 0.000872

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000932

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000863

Gnomad4 OTH exome AF: 0.00139

GnomAD4 genome AF: 0.00761 AC: 1159 AN: 152314 Hom.: 19 Cov.: 32 AF XY: 0.00740 AC XY: 551 AN XY: 74462

Gnomad4 AFR AF: 0.0268

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.00435 Hom.: 6

Bravo AF: 0.00842

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cataract 19 multiple types Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 23, 2023	- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.9
DANN	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs73933350; hg19: chr19-51890512;